title: Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease.
abstract: BACKGROUND
  Existing therapies for recurrent or refractory histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Rosai-Dorfman disease (RDD), have limited effectiveness. We report our experience with using clofarabine as therapy in children with recurrent or refractory histiocytic disorders, including LCH (11 patients), systemic JXG (4 patients), and RDD (3 patients).
  
  
  METHODS
  Patients treated with clofarabine for LCH, JXG, or RDD by Texas Children's Hospital physicians or collaborators between May 2011 and January 2013 were reviewed for response and toxicity.
  
  
  RESULTS
  Patients were treated with a median of three chemotherapeutic regimens prior to clofarabine. Clofarabine was typically administered at 25 mg/m(2) /day for 5 days. Cycles were administered every 28 days for a median of six cycles (range: 2-8 cycles). Seventeen of 18 patients are alive. All surviving patients showed demonstrable improvement after two to four cycles of therapy, with 11 (61%) complete responses, 4 (22%) partial responses, and 2 patients still receiving therapy. Five patients experienced disease recurrence, but three of these subsequently achieved complete remission. All patients with JXG and RDD had complete or partial response at conclusion of therapy. Side effects included neutropenia in all patients. Recurring but sporadic toxicities included prolonged neutropenia, severe vomiting, and bacterial infections.
  
  
  CONCLUSIONS
  Clofarabine has activity against LCH, JXG, and RDD in heavily pretreated patients, but prospective multi-center trials are warranted to determine long-term efficacy, optimal dosing, and late toxicity of clofarabine in this population.
authors.affiliation: Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Simko
authors.forename: Huy D
authors.initials: HD
authors.lastname: Tran
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jones
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Bilgi
authors.forename: Lynda Kwon
authors.initials: LK
authors.lastname: Beaupin
authors.forename: Don
authors.initials: D
authors.lastname: Coulter
authors.forename: Timothy
authors.initials: T
authors.lastname: Garrington
authors.forename: Timothy L
authors.initials: TL
authors.lastname: McCavit
authors.forename: Colin
authors.initials: C
authors.lastname: Moore
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivera-Ortegón
authors.forename: Linda
authors.initials: L
authors.lastname: Shaffer
authors.forename: Linda
authors.initials: L
authors.lastname: Stork
authors.forename: Lucie
authors.initials: L
authors.lastname: Turcotte
authors.forename: Esperanza C
authors.initials: EC
authors.lastname: Welsh
authors.forename: M John
authors.initials: MJ
authors.lastname: Hicks
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McClain
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy*; D015618:Histiocytosis, Sinus / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D012008:Recurrence; D016879:Salvage Therapy; D014972:Xanthogranuloma, Juvenile / Q000188:drug therapy*
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine
keywords: Langerhans cell histiocytosis; Rosai-Dorfman disease; clofarabine; histiocytosis; juvenile xanthogranuloma